Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder in Caucasians. Despite significant advances in medical therapy which have led to an increase in the median predicted age of survival from one year in 1950 to 40.7 years in 2013, the leading cause of mortality in CF patients remains respiratory failure due to pulmonary infection. Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important infectious pathogen in the CF population. The prevalence of MRSA pulmonary infection in the CF population has dramatically increased over the last twenty years, from less than 5% of patients in 1996 to 24.6% of patients in 2013. A series of studies completed by our group and others has shown that chronic and persistent MRSA infection is strongly associated with a more rapid decline in lung function and decreased survival in CF patients. However, there are no guidelines regarding treatment of MRSA infection in this population, nor have there been any completed randomized-control trials that examine treatment of persistent MRSA in CF patients. This study aims to investigate the safety and efficacy of inhaled vancomycin in treating persistent MRSA infection in CF patients. Inhaled antibiotics are a cornerstone of CF treatment for other pulmonary infections as this mode of administration allows the drug to be delivered directly to the site of infection. Intravenous vancomycin is one of the antibiotics most commonly used to treat MRSA infection. There have been multiple case reports suggesting that inhaled vancomycin is an effective method of treating pulmonary MRSA infection in both CF and non-CF populations, and that inhaled vancomycin is safe and well-tolerated. We have therefore initiated a randomized, double-blind, placebo-controlled trial studying inhaled vancomycin and its effects on the eradication of MRSA in patients with CF and persistent MRSA infection. We aim to enroll 40 patients at two clinical sites (Johns Hopkins Hospital and Case Western University Hospital) half of whom will receive our study drug and half who will receive taste-matched placebo for a 28-day time period. In addition to investigating the use of inhaled vancomycin in treating persistent MRSA infection in patients with CF, implementation of this proposal will provide training for the candidate that will be instrumental toward her career development and goal of becoming a clinician-scientist studying infection in cystic fibrosis.